Antisense mapping of MOR-1 in rats: distinguishing between morphine and morphine-6beta-glucuronide antinociception.

摘要: In an effort to correlate the recently cloned MOR-1 receptor with pharmacological actions of morphine and morphine-6β-glucuronide (M6G), we have used antisense paradigm. Rats were injected intracerebroventricularly (i.c.v.) oligodeoxynucleotides on days 1, 3 5 tested for analgesia day 6 after administration or M6G i.c.v. microinjection directly into either periaqueductal gray locus coeruleus. When given i.c.v., oligodeoxynucleotide targeting 5′-untranslated region exon 1 significantly decreased analgesic administered microinjected coeruleus, most profound inhibition occurring in gray. Thus, lateral ventricle can diffuse brainstem interfere actions. A mismatch same base composition which sequence four bases was changed inactive. This oligodeoxynucleotide, active against analgesia, failed block analgesia. contrast, sequences from exons 2 M6G, not morphine, The 4 slightly both antinociception. These results confirm mapping studies mice, implied presence a novel μ subtype responsible that may represent splice variant MOR-1. Unlike probe had small effect